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Telbivudine Versus Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B (TERESA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Young-Suk Lim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01595685
First received: May 8, 2012
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

The goal of chronic hepatitis B (CHB) treatment is complete and permanent eradication of hepatitis B virus (HBV) from patient's body, which is best represented by serum HBsAg loss accompanied by undetectable serum HBV DNA level.

While the most recently approved nucleos(t)ide analogues (NA) have marked antiviral potency and can induce HBV DNA undetectability in the majority of patients through prolonged treatment, NA need to be given long term, almost indefinitely, in most cases because they suppress HBV DNA only during therapy. For example, even after HBeAg-loss by a potent NA, suppression of serum HBV DNA to undetectable level is sustained only in about 23%-37% at 24 weeks off treatment. Thus, continuous therapy with NA until HBsAg clearance remains necessary in a majority of cases.

The recent availability of commercial quantitative assays of serum hepatitis B surface antigen (HBsAg) has enabled quantitative HBsAg to be used as a biomarker for prognosis and treatment response in CHB. It has been suggested that HBsAg decline during lamivudine or entecavir therapy is slower and less pronounced compared to interferon treatment, despite a higher effect on HBV DNA suppression. Based on HBsAg kinetics, it has been estimated that the predicted median time to HBsAg loss in patients treated with lamivudine or entecavir is more than 30 years. Thus, treatment that can induce rapid decline of HBsAg would have clear advantage in reducing the treatment duration required to achieve HBsAg-loss.

Interestingly, in a recent preliminary study, 24-weeks of treatment with telbivudine has induced HBsAg decline as comparable to pegylated interferon treatment. Although there has been no head-to-head trial comparing NAs in inducing HBsAg decline, previous studies consistently suggested that the decline of HBsAg is greater during telbivudine treatment compared with lamivudine or entecavir.

Thus, in this clinical trial, the investigators will investigate whether telbivudine is more effective in inducing HBsAg decline compared with entecavir in HBeAg-positive CHB patients who have achieved undetectable serum HBV DNA by preceding entecavir treatment.


Condition Intervention Phase
Chronic Viral Hepatitis B Without Delta-agent
Drug: Telbivudine
Drug: Entecavir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label Trial Comparing Telbivudine vs, Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B Who Have Achieved Serum HBV DNA Undetectability by Preceding Entecavir Treatment

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • HBsAg titer at 48 weeks [ Time Frame: at 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with serum HBsAg decline of ≥0.5 log10 IU/mL and <1.0 log10 IU/mL [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
  • Proportion of patients with serum HBsAg decline greater than 1.0 log10 IU/mL [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
  • Proportion of patients with serum HBsAg loss [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
  • Proportion of patients with serum HBeAg loss or HBeAg seroconversion [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
  • Proportion of patients with virologic rebound or genotypic resistance [ Time Frame: up to 48 weeks of treatment ] [ Designated as safety issue: Yes ]
  • Proportion of patients with normal ALT [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
  • Adverse events: Creatine kinase level, GFR, Muscle events, Other AEs [ Time Frame: up to 48 weeks of treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 184
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Telbivudine
Telbivudine 600 mg Daily Oral
Drug: Telbivudine
Telbivudine 600 mg Daily Oral
Other Name: Sebivo
Active Comparator: Entecavir
Entecavir 0.5 mg Daily Oral
Drug: Entecavir
Entecavir 0.5 mg Daily Oral
Other Name: Baraclude

Detailed Description:

A single-center randomized active-controlled open-label superiority trial

  • Patients will be randomly assigned 1:1 to receive telbivudine (600 mg/day) or ongoing entecavir (0.5 mg/day) for 48 weeks.
  • Eligible patients will be randomized using blocks of permuted treatment assignments after stratification by HBsAg level (1,000 IU/mL-5,000 IU/mL and ≥5,000 IU/mL IU/mL) and by entecavir treatment duration (1 year-2 year, ≥2 year).
  • Because over 98% of Korean patients with CHB have HBV genotype C,9 HBV genotype will not determined or be regarded as a stratification factor.
  • There will be no interruption in entecavir therapy before randomization.
  • Patients' treatment information will be retrospectively collected during entecavir treatment phase as well (DNA change, HBeAg status, HBsAg titre, ALT, and treatment duration. etc)
  • Patients will be screened within 4 weeks before randomization to determine study eligibility.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: All of below

  • HBsAg titer > 1,000 IU/mL
  • HBeAg positive at study entry and at the baseline of ETV treatment
  • HBV DNA undetectable (<15 IU/mL) at least 2 occasions of more than 3 months apart
  • Treatment with entecavir (0.5 mg/day) for more than 1 year
  • Patient is ambulatory.
  • Patient is able and willing to give informed consent.

Exclusion Criteria: Any of below

  • Prior exposure to oral nucloes(t)ide analogue other than entecavir
  • Prior any exposure to interferon or pegylated interferon
  • Cirrhosis with Child-Pugh score ≥8
  • Hepatocellular carcinoma Identified or suspected
  • Other malignancy
  • Prior organ transplantation
  • Under immunosuppressive agent
  • Renal insufficiency (serum creatinine > 1.4)
  • Pregnant woman or willing to be pregnant woman or man
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01595685

Contacts
Contact: Young-Suk Lim, M.D., Ph.D. +82-2-3010-5933 limys@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Principal Investigator: Young-Suk Lim, M.D., Ph.D.         
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Young-Suk Lim, M.D., Ph.D. Asan Medical Center
  More Information

No publications provided

Responsible Party: Young-Suk Lim, Associate Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01595685     History of Changes
Other Study ID Numbers: AMC2012-0201
Study First Received: May 8, 2012
Last Updated: January 15, 2014
Health Authority: Korea: Institutional Review Board

Keywords provided by Asan Medical Center:
HBeAg-positive

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Entecavir
Telbivudine
Anti-Infective Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014